Sodium Chloride → Methyl 4-amino-6-(2,5-difluoro-4-(trimethylsilyl)phenyl)-5-fluoro-3-methoxypicolinate

関与物質

反応手順

(2,5-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)trimethylsilane (1.785 g, 4.69 mmol, 82% purity), methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate (1 g, 4.26 mmol), Na2CO3 (0.542 g, 5.11 mmol), and PdCl2(PPh3)2 (0.299 g, 0.426 mmol) were suspended in a 3:1 mixture of CH3CN (7.99 mL) and H2O (2.66 mL) in a microwave vial. The reaction mixture was irradiated at 90° C. for 20 min. The reaction was monitored by TLC and ultra performance liquid chromatography (HPLC). The mixture was poured into a half satd aq NaCl solution and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (SiO2, ISCO, 120 g column, hexanes/EtOAc gradient) to afford the title compound as a yellow solid (0.977 g, 60%): mp 137-139° C.; 1H NMR (400 MHz, CDCl3) δ 7.23 (dd, J=7.9, 5.1 Hz, 1H), 7.12 (dd, J=9.3, 4.0 Hz, 1H), 4.60 (s, 2H), 3.97 (s, 3H), 3.97 (s, 3H), 0.33 (d, J=0.8 Hz, 9H); 19F NMR (376 MHz, CDCl3) δ −107.12, −121.88, −137.27; ESIMS m/z 384 ([M]+).

情報源と証拠